This webinar, presented by Professor Stephen Senn, explored the principles underpinning the design of N-of-1 trials involving multiple participants. The session introduced the history and rationale for N-of-1 methodology, examined how sets of N-of-1 trials can be used to estimate average treatment effects across individuals, and discussed key design considerations including treatment allocation, randomisation strategies and fixed linear models. The webinar formed the first part of a two-part series and is complemented by the follow-up webinar on the analysis and planning of N-of-1 trials.